tbuckley/cabot-search huggingface dataset:
A funder-based comparison of global oncology research led by NCI-designated cancer centers: Results from the 2021 global oncology survey.
Authors: Elise M. Garton, Linsey Eldridge, Mishka K. Cira, Allison Frank, Patrick J. Loehrer, Kalina Duncan
Journal: Journal of Clinical Oncology (2023)

e18535 Background: Equitable global cancer research partnerships are key to reducing the global burden of cancer, which disproportionately affects low-and middle-income countries (LMICs). One indicator of equitable partnerships is the inclusion of LMIC investigators in global cancer research. In 2021 the National Cancer Institute (NCI) conducted a survey of the 71 NCI-Designated Cancer Centers about their global oncology activity. The survey results highlight cancer centers' non-NIH funded global cancer research, training, and capacity-building projects and complement data about global cancer research funded by the National Institutes of Health (NIH). This analysis presents NIH and non-NIH funded global oncology research led by cancer centers stratified by collaborator income class. Methods: NCI designed and fielded an online survey to cancer center global oncology contacts and principal investigators of research projects from July 2021 through January 2022. Data about NIH grants were sourced from internal NIH systems. Income classes are defined by the World Bank and analysis was conducted in Microsoft Excel and Python. A two proportion Z test was used to test for differences in collaborator income class between NIH grants and non-NIH funded projects. Results: Ninety-four percent (67/71) of cancer centers responded to the survey. Forty-seven cancer centers reported 257 global oncology projects with named international collaborating institutions in 2021. Comparatively, 69 cancer centers held 688 NIH cancer research grants with international collaborating institutions in 2021. These projects and grants had collaborators in 111 countries, including 72 LMICs. Projects and grants were stratified by whether they had collaborators only in high-income countries (HICs), only in LMICs, or in both HICs and LMICs, as shown in Table 1. Non-NIH funded global oncology projects were significantly more likely than NIH grants to have only LMIC collaborators (p = 0.0006) or both HIC and LMIC collaborators (p &lt; 0.0001). Conclusions: While the inclusion of LMIC collaborators in research does not guarantee an equitable partnership nor effective research, it is one indicator of these efforts. The results of the global oncology survey demonstrate that cancer centers are committed to conducting research in LMICs and with LMIC institutions, and they are more likely to collaborate with LMIC institutions when supported by a non-NIH funder or by institutional funds. Further analysis is recommended to understand the extent to which research collaboration indicates equitable partnership, and the barriers and facilitators to collaboration posed by different funding sources. [Table: see text]
The performance of prostate specific antigen (PSA) testing in the population based NPCC cohort.
Authors: Jan Oldenburg, Johan Lars Bjerner, Lara Pasovic, Stig Müller, Sophie D. Fossa, Sigrid V. Carlsson, Peter C. Albertsen
Journal: Journal of Clinical Oncology (2023)

5029 Background: Prostate cancer (PCa) screening using prostate-specific antigen (PSA) is controversial. Benign prostate hyperplasia increases PSA in aging men independent of PCa such that PSA’s test performance differs between younger and older men. Age-specific cut-off values might therefore be advisable. The large Norwegian Prostate Cancer Consortium (NPCC) database might be able to contribute with clinically relevant information on age-specific PSA cut-off values. Methods: The Norwegian Prostate Cancer Consortium (NPCC) collected 8 857 761 PSA tests from 1.291.151 men. Results were linked with the date of diagnosis and grade of PCa. Analyses were restricted to men aged 45-75 years. PSA results were grouped into two groups: PCa negative vs PCa positive. The PCa negative group comprised PSA measurements from 2005 to 2015 men being alive and without PCa diagnosis five years after PSA measurement, in total 1 775 986 PSA measurements from 533 216 men. The PCa positive group comprised PSA measurements from 2005 to 2020 of men diagnosed with PCa during this period. PCa diagnoses at autopsy, as incidental finding at cystectomy, with metastases or with PSA &gt; 50 ng/ml were excluded, in total 242 874 PSA measurements from 48 659 men with PCa. Sensitivity, specificity, area under the curve (AUC) as well as top decile and proportion of PCa in the top decile were calculated. Results: For men of 50 years of age, PSA at a threshold of 3 ng/ml yielded a sensitivity and specificity of ~ 95%. In 70–74-year-old men, a 3 ng/ml PSA threshold resulted in a 95% sensitivity but declining specificity of 70%. Maintaining specificity requires increasing PSA cut-off values to 4.5, 6, 7 and 8 ng/ml for men aged 55-59, 60-64, 65-69 and 70-74 years, respectively. The increasing cut-off values for the top PSA decile as well as the decreasing proportion of PCA within the top decile are in line with a declining AUC in older men. Conclusions: PSA test performance declines with increasing age. PCa screening in well-informed men should take into account age adjusted PSA cut-off values. [Table: see text]
Patient-reported outcomes (PROs) among men receiving talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA as first-line (1L) treatment for metastatic castration-resistant prostate cancer (mCRPC): Results from a phase 3 study (TALAPRO-2).
Authors: Neeraj Agarwal, Arun Azad, Nobuaki Matsubara, Fred Saad, Ugo De Giorgi, Jae Young Joung, Peter C.C. Fong, Robert J. Jones, Stefanie Zschaebitz, Jan Oldenburg, Neal D. Shore, Curtis Dunshee, Joan Carles, Andre P. Fay, Paul Cislo, Jane Chang, Cynthia G. Healy, Alexander Niyazov, Karim Fizazi
Journal: Journal of Clinical Oncology (2023)

5013 Background: TALAPRO-2 (NCT03395197) showed statistically significant improvement in radiographic progression free survival with TALA + ENZA (n=402) vs PBO + ENZA (n=403) (HR=0.63 95% CI 0.51-0.78; P&lt;0.001) in men receiving 1L treatment for mCRPC. Here we report PRO endpoints from TALAPRO-2. Methods: PROs were assessed at day 1 (baseline) and at scheduled visits until radiographic progression (every 4 weeks until week 53, and then every 8 weeks) using the EORTC QLQ-C30 and its prostate cancer module, QLQ-PR25. Prespecified PRO analyses included overall mean change from baseline (per longitudinal repeated measures mixed-effects model) and time to definitive clinically meaningful (≥10-point change) deterioration (TTD). Between-arm comparisons of TTD were made using a stratified log-rank test and a Cox proportional hazards model. Results: Of the 805 men randomized and treated, 793 had a baseline score followed by at least 1 post-baseline score; TALA + ENZA (n=395), PBO + ENZA (n=398). Although the treatment effect on global health status (GHS)/quality of life (QoL) significantly favored PBO + ENZA, the predefined threshold of clinical meaningfulness was not met; moreover, no significant differences between the arms were observed in any functioning scales. A significantly longer TTD in GHS/QoL was observed for TALA + ENZA; HR=0.780 (95% CI: 0.62, 0.99), P=0.038; median: 30.8 months vs 25.0 months. A numerical greater delay in TTD in urinary symptoms was longer for TALA + ENZA; HR=0.759 (95% CI: 0.543, 1.061), P=0.105; median not reached vs 35.9 months. Additional PRO results will be presented. Conclusions: Compared with PBO + ENZA, in the TALA + ENZA arm there was 1) a modest deterioration disfavoring GHS/QoL (deterioration was not clinically meaningful based on the predefined threshold), and 2) a maintenance in all functioning scales. TTD in GHS/QoL was significantly longer with TALA + ENZA vs PBO + ENZA, reflecting improved disease control. These results complement the benefit-risk assessment of TALAPRO-2. Clinical trial information: NCT03395197 . [Table: see text]
Prediction of 6-year risk of bladder cancer using the HUNT Lung Cancer Risk Model in ever-smokers: A HUNT study.
Authors: Oluf D. Røe, Olav Toai Duc Nguyen, Yannis Fotopoulos, Vincenzo Lagani, Ioannis Tsamardinos
Journal: Journal of Clinical Oncology (2023)

e16581 Background: Bladder cancer is the 6th most common cancer in men and 17th most common cancer in women and the mortality is high when detected in advanced stage. Previous or current cigarette smoke is the main risk factor. There is no screening program for bladder cancer. Given the pathophysiological similarity with lung cancer, we postulated that a lung cancer risk model could work for bladder cancer. The validated HUNT Lung Cancer Risk Model (HUNT LCM) predicts lung cancer in 6 years with an area under the ROC curve (AUC) of 0.87. Here we aimed to test the performance of the HUNT LCM in the prospective HUNT2 cohort for a 6-year prediction of bladder cancer. Methods: The HUNT2 cohort from Norway, a prospective population study of 65 200 individuals 19-100 years of age, was followed up for a median of 15 years. This population was linked with the Norwegian Cancer Registry and all cases diagnosed with bladder cancer were registered. The HUNT Lung Cancer Model was used to predict risk of bladder cancer within 6 years. Results: In the HUNT2 cohort 38 846 ever-smokers were identified. 82.6% of those developing bladder cancer were ever-smokers. 31 269 had all the variables needed for the model and of those, 191 developed bladder cancer in six years. The HUNT Lung Cancer Model prediction of bladder cancer in 6 years AUC was 0.751. Conclusions: To our knowledge, this is the first time a lung cancer risk prediction model has been applied to predict bladder cancer. The performance of the model is lower than for lung cancer but still has a good performance. This may open a path for screening and early detection of bladder cancer.
Efficacy and safety of combining PD-1 blockage and human papillomavirus vaccine for patients with relapsed/refractory advanced cervical cancer.
Authors: Buhai Wang, Juan J Gu, Yuechao Wu, Yichun Zeng, Yichen Liang, Liqin Liu, Yinxia Wu, Yuxiang Huang, Qiuxian Li, Caiyue Chen
Journal: Journal of Clinical Oncology (2023)

5530 Background: The prognosis for patients with relapsed/refractory advanced cervical cancer is dismal with a 5-year survival rate of 17%. Limited treatment options were available including platin based therapy, antiangiogenic therapy and immune therapy. Immune checkpoint blockage with anti-programmed cell death 1 (PD-1) antibodies had an overall response rate of 17% among a minority of patients. Recently a phase II study showed human papillomavirus (HPV) 16 vaccination amplified PD-1 antibodies in incurable HPV16 positive cancer with an ORR of 33%. But the study enrolled majority were oropharyngeal cancer patients (92%). Here, we designed and conducted phase II clinical trial to assess the efficacy and safety of combining anti-PD-1 antibody and HPV vaccination for patients with relapsed/refract cervical cancer. Methods: In this single-arm, single-center phase II clinical trial, patients with relapsed/refract cervical cancer were registered (NCT04096911) and enrolled from Dec, 2019 to Dec, 2022 in Department of Oncology, Northern Jiangsu People's Hospital, Yangzhou, China. All patients received prior radiation therapy and had at least one or more lines of therapies. Duration of follow up for censored patients was 36 months. The recombinant human papillomavirus quadrivalent vaccine (0.5ml) was given subcutaneously on day 0, third month, and 6 th month. Anti-PD-1 antibody, 200mg was given intravenously every 3 weeks starting on day 1 for up to 2 years. Results: As of Dec 21, 2022, thirteen patients were enrolled in the trial. The median age was 55 years (range, 52 to 83 years). The overall response rate was 69.2%. Disease control rate was 84.9%. Median duration of response was 7.07 months (95%CI, 1.94 to 15.8 month). Six patients achieved complete response. Median overall survival was 13.96 month. No grade 3 and 4 toxicity occurred. Conclusions: Our study was the first clinical trial using HPV vaccine as therapeutic agent in advance cervical cancer treatment. Up to date, immunotherapy along in cervical cancer had limited response rate less than 20% and the combination therapies was less than 40%. In our study, the overall response of 69.2%, disease control rate of 84.9% and median overall survival of 13.96 months were significantly higher compared with anti-PD-1 antibody alone or any current available regiment combinations in relapsed/refract advance cervical cancer patients. We also found synergistic effect of T cell and B cell plays an important role in our study. It appears neoantigen associated with tumor was easier to initiate immune response in cervical cancer patients. This is the first time to show employing combined immune therapeutic agents only is a novel effective clinical strategy in relapsed/refract advance cervical cancer. Clinical trial information: NCT04096911 .
Real-world data for predictors of PSA response to Lu177-PSMA-617 in metastatic castration resistant prostate cancer.
Authors: Rebecca Hassoun, Mark Tann, Justin Sims, Ashleigh Auxier, Sandra K. Althouse, Jennifer King, Nabil Adra
Journal: Journal of Clinical Oncology (2023)

e17044 Background: Lu177-PSMA-617 (Lu177) therapy is effective in a subgroup of patients with metastatic castration resistant prostate cancer (mCRPC). We evaluated PSA responses in subgroups of pts with mCRPC. Methods: Pts with mCRPC who progressed after androgen receptor pathway inhibitor (ARPI) and taxane chemotherapy (or who have refused chemotherapy) were treated with Lu177. Pts with ≥6 weeks follow-up after start of Lu177 therapy were included. Baseline clinical/molecular characteristics and PSMA PET parameters were analyzed and association with PSA30 response was evaluated. Results: 45 pts were included. Median age 71.7 (range, 58-90). At baseline PSMA PET: 37 pts had PSMA + disease in bone, 28 lymph nodes, 5 lungs, 4 liver, and 1 brain. 14 pts had 1 prior ARPI, 31 pts had ≥2 prior ARPI. 5 pts had no prior taxane regimen, 18 had 1 prior taxane, 14 had 2 prior taxanes and 8 had ≥3 taxane regimens. 10 pts had prior PARP inhibitor. With a median follow-up of 2.8 months (1.4-6.1) from starting Lu177 therapy, 21 (46.7%) pts achieved a PSA30 response, and 18 (40.0%) pts achieved a PSA50 response. 24 (53.3%) pts achieved any confirmed PSA response. Grade≥3 toxicity occurred in 3 pts. Conclusions: There is a trend with higher PSA30 and PSA50 response to Lu177 with higher SUVmean, less prior taxane exposure, and in pts with homologous recombination repair mutations (HRR). [Table: see text]
Real-world use, dose intensity, and adherence to enfortumab vedotin (EV) in locally advanced or metastatic urothelial cancer (la/mUC).
Authors: Konstantinos Tsingas, Ravi Bharat Parikh, Dina Elsouda, Lisa Mucha, Rupali Fuldeore, Rebecca A. Hubbard, Ronac Mamtani
Journal: Journal of Clinical Oncology (2023)

e16567 Background: EV, the first antibody drug conjugate approved for la/mUC, received accelerated approval in the US in 2019 as later-line therapy (post-immunotherapy and platinum-chemotherapy) and regular approval in 2021 with label expansion to include earlier-line therapy (cisplatin-ineligible, ≥1 prior therapy). Because EV delivery per current labelling (1.25 mg/kg, D1, 8, 15 of a 28D cycle) may differ from routine practice, we examined real-world EV use, dose intensity and adherence across 280 US cancer clinics. Methods: This descriptive post-marketing retrospective cohort study used the Flatiron Health longitudinal database derived from EHR records of US patients with la/mUC initiating EV on or after December 19, 2019. We summarized EV use, including but not limited to: % cisplatin-ineligible, and median duration of use and number of cycles administered. We computed metrics of dose intensity: average treatment rate (mean number of treatments per patient-month), dosing frequency (mean number of treatments per cycle), dose (mean dose, mg/kg), and % change in dose (mg) from baseline (difference in dose between last recorded treatment in last cycle and first recorded treatment in first cycle). Finally, we measured treatment adherence, defined as % of cycles across all patients where a patient had &gt; 2 treatments per 28D cycle. Results: Among patients with la/mUC, we identified 416 EV users (mean [SD] age 71 [9] years, 27.4% female, 24.8% non-white, 70.2% prior smokers, 17.5% ECOG 2+, 81.5% from community sites). EV use, dose intensity, and adherence are shown (table). Most were cisplatin-ineligible (55%). Average dosing frequency (2.4 [0.5] treatments per cycle) and dose (1.1 [0.2] mg/kg) were lower than label indication guidelines; 58.8% received &gt; 2 treatments per 28D cycle. Conclusions: Among la/mUC patients treated with EV in contemporary practice, treatment frequency and dosing were lower than recommended in the product labelling. Further research is required to understand clinical factors and outcomes associated with the differences observed. [Table: see text]
Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma (AM) in patients with concomitant chronic lymphocytic leukemia (CLL).
Authors: Samuel Cass, Joshua Tobin, Yongwoo David Seo, Georgina Gener-Ricos, Emily Zhi-Yun Keung, Elizabeth M. Burton, Danielle M. Walsh, Michael A. Davies, Jennifer Leigh McQuade, Alexander J. Lazar, Paul Joseph Hampel, Jennifer Ann Wargo, Alessandra Ferrajoli
Journal: Journal of Clinical Oncology (2023)

e19511 Background: CLL is the most prevalent adult leukemia and is associated with an increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICI in patients with CLL. Immune checkpoint inhibitors (ICI) have revolutionized management of AM, but data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. We, therefore, sought to examine the efficacy of ICI for melanoma in patients with concomitant CLL and AM. Methods: In this international and multicentre retrospective study, review of clinical databases identified patients with concomitant CLL and AM treated with ICI from two US tertiary cancer centers (n = 39) and an Australian multi-institutional experience (AUS, n = 19). Objective response rates (ORR), defined as complete or partial response by RECIST v1.1, and survival outcomes (overall survival, OS, and progression-free survival, PFS) among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Results: Between 1997 and 2020, 58 patients with CLL were treated with ICI for concomitant AM. Among all patients with CLL and AM, ORR to ICI was 41% and median duration of response was 18 months. A majority were untreated for CLL (64%) at the time of ICI. Patients with prior history of treatment for CLL had significantly reduced ORRs (21% vs 51%, p = 0.04), PFS (3.6 vs. 14.6 months, p = 0.005), and OS (7.4 vs. 52.2 months, p = 0.002), compared to patients on observation for their CLL. Prior treatment with T-lymphocyte depleting chemoimmunotherapy (fludarabine, bendamustine, and alemtuzumab) was particularly associated with poor outcomes (median OS of 7.0 months, median PFS of 3.4 months). On univariate analysis, prior treatment for CLL, high risk CLL 17p deletion, and higher CLL Rai stage were associated with shorter PFS from ICI, though CLL treatment was the only factor independently associated with shorter PFS in the multivariate model (HR 6.5, [CI 2.1-20.3], p = 0.001]. Overall, 3 patients developed CLL progression while on ICI, though in two of these patients, the AM had an objective, durable clinical response to ICI. Overall, immune-related adverse events (irAE) occurred following 38% of ICI and rates of irAE were similar by CLL treatment status. Conclusions: Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.
A phase 1 clinical trial of DB-020 intratympanic injections administered prior to high dose cisplatin chemotherapy to reduce ototoxicity.
Authors: Danny Rischin, Stephen John O'Leary, Christopher David Hart, Chandra Sai Diwakarla, Nagashree Seetharamu, John Lee, Shane Raines, Tera Quigley, Heather M Wolff, Pablo Lapuerta, Benedict J Panizza
Journal: Journal of Clinical Oncology (2023)

6043 Background: Hearing loss with cisplatin (CP) chemotherapy is common. DB-020 is a formulation of thiosulfate for intratympanic (IT) injection being developed to reduce CP ototoxicity. The primary objective of this Phase 1 study was to evaluate the safety and tolerability of repeated IT injections of DB-020. A secondary objective was to compare hearing changes with DB-020 vs. placebo. Methods: Subjects scheduled for at least 3 cycles of CP and cumulative exposure of ≥280 mg/m 2 were randomized to blinded, bilateral, IT injection with DB-020 (12% or 25%) in one ear and placebo in the other, once every 3 or 4 weeks, up to 3 hours before receiving CP. Subjects with moderate or severe hearing loss at baseline were excluded. Ototoxicity was defined by American Speech-Language-Hearing criteria: ≥20 dB threshold increase at any one test frequency, or ≥10 dB threshold increase in any two adjacent frequencies, or loss of response at three consecutive frequencies where responses were previously obtained. Severe ototoxicity was ≥20 dB threshold increase in any two adjacent frequencies. A pre-specified interim analysis evaluated safety, ototoxicity (with Mcnemar’s test using the last observation carried forward), and average threshold shifts (from air conduction audiometry, analyzed with a mixed model with repeated measures). Results: Nineteen subjects were randomized, with mean age of 57 years (84% male and 100% white) and mean cumulative CP dose 248 mg/m 2 . Most (95%) had head and neck cancers (5% had lung cancer). Seventeen subjects had both baseline and follow-up audiometry, and 16/17 had baseline audiograms within 5 dB of the median threshold for age-matched controls. Free CP systemic levels were similar to reference values. Ear pain (15/19 subjects, 78.9%) and tinnitus (8/19 subjects, 42.1%) were common. Ear pain was more common in DB-020 treated ears, and tinnitus was more common in placebo treated ears. There were no tympanic perforations, no serious adverse events in the category of ear and labyrinth disorders, and no deaths. Ototoxicity was significantly more common and more severe in placebo treated ears (Table). As the overall study objectives were met at this interim analysis, no further enrollment was pursued. Conclusions: In this initial clinical trial experience there was no significant safety signal, and DB-020 IT injections showed a meaningful reduction in cisplatin ototoxicity. These results warrant further clinical development. Clinical trial information: NCT04262336 . [Table: see text]